Defensins are the predominant immune peptide produced by Aedes aegypti in response to microbial insult, and a growing amount of data suggest this molecule, either alone or in concert with other immune factors, can interfere with the development of filarial worms and malaria parasites, if the defensin gene is induced early in an infection. To address the overall hypothesis that defensins and the antimicrobial humoral response of mosquitoes can limit the development of eukaryotic parasites, the following specific aims are proposed: (1) To identify and characterize those mechanisms regulating gene expression of defensins in Ae. Aegypti, with the long-term goal of determining how parasites are able to avoid turning on this immune response; (2) to evaluate the biology of defensins regarding their temporal and spatial expression patterns, the potential existence of a primitive immunological memory system, and their ability to kill eukaryotic parasites in vitro and in vivo; (3) to use sequence data available for immune peptides in Aedes and Anopheles mosquitoes to begin the isolation and characterization of immune peptides in Culex and to determine if immune activation limits the development of Wucheria bancrofti in this natural vector; and, (4) to use transducing viruses and transposon-mediated transformation to critically evaluate the ability of defensins and/or other immune peptides to kill filarial worms and malaria parasites in Ae. aegypti and Cx. pipiens. Studies with Cx. Pipiens and W. bancrofti are possible because of a collaborative arrangement with researchers in Egypt.